Submissions for variant NM_000249.4(MLH1):c.1342G>T (p.Glu448Ter)

dbSNP: rs1575537933

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001010969	SCV001171239	pathogenic	Hereditary cancer-predisposing syndrome	2017-01-24	criteria provided, single submitter	clinical testing	The p.E448* pathogenic mutation (also known as c.1342G>T), located in coding exon 12 of the MLH1 gene, results from a G to T substitution at nucleotide position 1342. This changes the amino acid from a glutamic acid to a stop codon within coding exon 12. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV001823177	SCV002072880	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2		criteria provided, single submitter	clinical testing	The stop gained p.E448* in MLH1 (NM_000249.4) has been previously reported in affected. The p.E448* variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function mutations have been reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV001823177	SCV004189941	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-20	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.